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Role of the Microbiome in Graves' Orbitopathy (Indigo)

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ClinicalTrials.gov Identifier: NCT02373995
Recruitment Status : Unknown
Verified February 2015 by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico.
Recruitment status was:  Not yet recruiting
First Posted : February 27, 2015
Last Update Posted : February 27, 2015
Sponsor:
Collaborators:
Cultech Ltd, Port Talbot, UK
Universität Duisburg-Essen
School of Medicine and School of Biosciences, Cardiff University, Cardiff, UK
IDRA Laboratory, Parco Tecnologico Padano s.r.l, Lodi, Italy
Information provided by (Responsible Party):
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary:
Graves' orbitopathy (GO), also known as thyroid eye disease, affects approximately 3 million people in Europe with an estimated socioeconomic burden of 6.4 billion euros per annum. GO is a complication of Graves' disease which is an autoimmune disease and the commonest cause of an overactive thyroid gland. The treatment of GO remains unsatisfactory and the majority of patients report long-term impairment of quality of life. The effects of gut derived antigens, from micro-organisms and nutrients, on the autoimmune response will be tested in the animal model by probiotic and "contra-biotic" intervention. In the Indigo interventional trial the investigators will add to the standard anti-thyroid drug treatment (ATD) a specifically designed probiotics (LAB4, Cultech Ltd., West Glamorgan, UK) to assess whether it is possible to modify the microbiome in GD patients and improve their immunological status.

Condition or disease Intervention/treatment Phase
Graves' Disease Biological: LAB4 Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Investigation of Novel Biomarkers and Definition of the Role of the Microbiome In Graves' Orbitopathy
Study Start Date : February 2015
Estimated Primary Completion Date : July 2015
Estimated Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: LAB4
In addition to conventional Anti Thyroid Drug (ATD), LAB4 probiotic preparation will be administered at the 2 cps x 2/die dosing with food for 6 months. It is key to properly store LAB4 at 8°C.
Biological: LAB4
Additional treatment with the specific LAB4 probiotic preparation

Placebo Comparator: Placebo
In addition to conventional Anti Thyroid Drug (ATD) a LAB4 placebo preparation will be administered at the 2 cps x 2/die dosing with food for 6 months. It is key to properly store placebo at 8°C.



Primary Outcome Measures :
  1. Microbiome modification (beneficial modification of the gut microbioma relates to a reduction at the end of treatment of at least 5% of the Firmicutes:Bacteroides ratio and 30% of the anti-TSHr antibody titer and of total IgG and IgA concentrations) [ Time Frame: 6 months ]
    modification the microbiome in GD patients to reduce pathogenic species and enrich its commensal, symbiotic components. The proportion (%) of each species will be assessed and recorded.


Secondary Outcome Measures :
  1. Improvement immunological status (antibody responses will be analyzed to identify if microbial or food derived antigens are involved in triggering disease or associated with GO progression) [ Time Frame: 6 months ]
    To decrease the anti-TSHr antibody titer and the concentration of IgG and IgA in patients with Graves' disease. The concentration of each parameter will be assessed in mg/dl and recorded.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Group A: Untreated Graves' hyperthyroidism (or within 4 weeks of initiating ATD treatment)
  • definition hyperthyroidism: TSH decreased, FT4 and /or FT3 increased
  • definition Graves': diffusely enlarged thyroid gland either by palpation or echograpy, and/or homogeneous thyroid uptake at scintigraphy, or positive TSHRAb
  • first episode or recurrence of Graves' hyperthyroidism
  • minimal or no eye signs, defined as lid retraction / lid lag but no other signs.

Planned treatment with antithyroid drugs either titration regimen or block-and-replace regimen for 18 months.

Group B. Untreated Graves' hyperthyroidism (or within 4 weeks of initiating ATD treatment) with overt signs of GO as defined by EUGOGO1

  1. Mild GO: patients whose features of GO have only a minor impact on daily life insufficient to justify immunosuppressive or surgical treatment. They usually have only one or more of the following: minor lid retraction (<2 mm), mild soft tissue involvement, exophthalmos <3 mm above normal for race and gender, transient or no diplopia, and corneal exposure responsive to lubricants)
  2. Moderate-to-severe GO: Patients without sight-threatening GO whose eye disease has sufficient impact on daily life to justify the risks of immunosuppression (if active) or surgical intervention (if inactive). Patients with moderate-to-severe GO usually have any one or more of the following: lid retraction R2 mm, moderate or severe soft tissue involvement, exophthalmos >3 mm above normal for race and gender, inconstant, or constant diplopia.
  3. Sight -threatening GO: Patients with dysthyroid optic neuropathy (DON) and/or corneal

Exclusion Criteria:

  • Previous or planned treatment with 131I or thyroidectomy (A&B); sight threatening GO requiring decompression (B); drugs interfering with the natural course of GO (A&B): steroids, immunosuppressants, thiazolidinediones, antibiotics / antifungals / antivirals (both topical and systemic for at least 4 weeks prior to recruitment to the study); acute diarrhea illness (gastroenteritis for at least 4 weeks prior to recruitment to the study); Drugs interfering with thyroid function (A&B): amiodarone, lithium, iodine supplements; Drug or alcohol abuse (A&B); no informed consent (A&B); Age less than 18 (A&B); Pregnancy (A&B).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02373995


Contacts
Contact: Mario Salvi, MD +393487362498 mario@mariosalvinet.it
Contact: Giuseppe Colucci, MD +393486510071 coluccg1@gmail.com

Locations
Italy
Fondazione Ca' Granda Ospedale Maggiore Policlinico
Milan, Italy, 20122
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Cultech Ltd, Port Talbot, UK
Universität Duisburg-Essen
School of Medicine and School of Biosciences, Cardiff University, Cardiff, UK
IDRA Laboratory, Parco Tecnologico Padano s.r.l, Lodi, Italy
Investigators
Principal Investigator: Mario Salvi, MD IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano

Publications of Results:
Responsible Party: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier: NCT02373995     History of Changes
Other Study ID Numbers: Indigo
First Posted: February 27, 2015    Key Record Dates
Last Update Posted: February 27, 2015
Last Verified: February 2015

Keywords provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Graves
Orbithopaty
euthyroidism
microbiome

Additional relevant MeSH terms:
Graves Disease
Exophthalmos
Orbital Diseases
Eye Diseases
Goiter
Thyroid Diseases
Endocrine System Diseases
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases